What Researchers Actually Did

Investigators extracted de-identified administrative claims and linked laboratory data from the Komodo Research Database, a nationally representative U.S. repository spanning January 2016 through December 2024. Eligible participants were adults aged 45 years or older with documented overweight or obesity — confirmed by ICD-10-CM codes or anthropometric records reflecting BMI ≥27.0 kg/m² — and with prior evidence of clinical ASCVD according to the 2018 AHA/ACC definition. That definition is broader than the one used in the SELECT trial: it encompasses not only prior MI, ischemic stroke, and peripheral arterial disease, but also stable angina, unstable angina, transient ischemic attack (TIA), carotid stenosis, and aortic aneurysm. Patients with any history of diabetes, end-stage kidney or heart failure, pancreatitis, bariatric surgery, or prior GLP-1 or GIP/GLP-1 receptor agonist use for weight management were excluded. The index date for the semaglutide 2.4 mg cohort was the date of the first qualifying pharmacy claim; for the non-use cohort, an index date was randomly assigned from the post-approval period. A minimum of 12 months of continuous insurance enrollment before the index date was required.

To address confounding, investigators built a non-parsimonious propensity score model incorporating more than 70 baseline demographic and clinical variables — including ASCVD phenotype, comorbidities, medications, healthcare utilization, and insurance type — and matched each semaglutide 2.4 mg user to up to two non-users via greedy nearest-neighbor matching within a caliper of 0.2 standard deviations of the logit of the propensity score. After matching, all standardized mean differences were below 0.1, indicating adequate covariate balance. Outcomes were identified using ICD-10-CM diagnosis codes (primary position on inpatient visits for MI, stroke, and HF hospitalization) and procedure codes for revascularization. All-cause mortality was captured by month and year, with the date assigned as the last day of the recorded month. Competing risks were handled using Aalen-Johansen

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